This invention relates to hydroxy and alkoxy substituted pyridines, more particularly, to 2-substituted amino 5-(hydroxy or alkoxy) pyridines and acyl derivatives thereof. The compounds of this invention are inhibitors of leukotriene syntheses and are therefore useful in the treatment of pulmonary, inflammatory, dermatological, allergic and cardiovascular diseases.
Watnick et al., Arch. Int. Pharmaeodyn., 190, 78-90 (1971), refer to the anti-inflammatory and analgesic properties of clonixin (2-(2'-methyl-3'-chloroanilino) nicotinic acid).
Nantha et al., Acta Pol. Pharm., 33(1), 7-11(1976), refer to certain derivatives of 2-anilino-5-hydroxynicotinic acid, including 6-methyl-2-anilino-5-hydroxynicotinic acid.
Shen et al., in U.S. Pat. No. 4,038,396, refer to the anti-inflammatory properties of certain oxazolo[4,5-b]pyridines.
Moore et al., J. Org. Chem., 32, 1353-1360 (1966) refer to the production of certain 2-carbonylamino-3-phenyl-4-methyl-5-hydroxy pyridines by heating unsaturated acyldiazabicyclic ketones in methanol.
Moore et al., J. Org. Chem., 30, 1887-9 (1964), refer to the production of 2-methylamino-3-phenyl-4-methyl-5-hydroxy pyridine by heating 2,5-dimethyl-4-phenyl-2,3-dihydro-6H-diazapin-6-one in a base.
Lombardino et al., J. Med. Chem., 24, 39-42 (1981), refers to 2-amino-5-methoxy pyridine as an intermediate in the synthesis of certain metabolites of the anti-inflammatory agent piroxicam.
Current treatment of asthma focuses on the relief of acute bronchospasm through the use of bronchodilators. It is thought that acute bronchospasm is only an overt manifestation of chronic inflammation. Leukotrienes may play a role both in the bronchospasm and the chronic inflammation. They are known to be potent vasodilators and chemotactic agents. They are also produced in allergic reactions and bring about slow contraction of lung tissue in vitro. An inhibitor of leukotriene synthesis should therefore be of use in the treatment of asthma and other pulmonary diseases.
Chronic gastric and duodenal ulcers, together known as peptic ulcers, are the subject of a variety of treatments, including special diets, drug therapy and surgery, depending upon the severity of the condition. Particularly valuable therapeutic agents useful for the treatment of gastric hyperacidity and peptic ulcers are the histamine-H.sub.2 receptor antagonists, which block the action of the physiologically-active compound histamine at the H.sub.2 -receptor sites in the animal body and thereby inhibit the secretion of gastric acid.